Oral diseases · 2025
LncRNA FENDRR Inhibits Mitochondrial Apoptosis via TET2-Mediated DNA Demethylation of MFN1 in NSCPO.
СтатьяНазвание и аннотация: Перевод в очереди
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Wu Caihong, Liu Haojie, Shan Zerui, Xia Yu, Zhao Panpan, Zhang Zhongyin, Yueguang Gu, Ma Junqing
Аннотация
BACKGROUND: Non-syndromic cleft palate only (NSCPO) and non-syndromic cleft lip with or without cleft palate (NSCL/P) are distinct malformations with different or partially overlapping etiologies. While NSCL/P has been extensively studied, NSCPO remains relatively understudied. Emerging evidence suggests that long noncoding RNAs (lncRNAs) contribute to craniofacial development, potentially by regulating apoptosis.
METHODS: This study investigated the role of FENDRR, a lncRNA previously found to be downregulated in NSCL/P, in NSCPO pathogenesis. FENDRR expression in NSCPO tissues was analyzed via RT-qPCR and fluorescence in situ hybridization. Apoptosis in human embryonic palatal mesenchymal (HEPM) cells was assessed using Western blotting, flow cytometry, and TUNEL assays. Bioinformatics, methylation-specific PCR, dual-luciferase reporter assays, and RNA immunoprecipitation were employed to examine FENDRR's interaction with MFN1.
RESULTS: FENDRR was significantly reduced in NSCPO tissues. FENDRR knockdown disrupted mitochondrial dynamics and activated mitochondrial apoptosis in HEPM cells. Mechanistically, FENDRR formed an RNA-DNA triplex with the MFN1 promoter, recruiting TET2 to promote MFN1 transcription via promoter demethylation.
CONCLUSIONS: FENDRR enhances MFN1 expression, maintains mitochondrial fusion, and suppresses apoptosis in HEPM cells. This study provides novel insights into the regulatory role of lncRNAs in NSCPO pathogenesis and identifies FENDRR as a potential therapeutic target.
METHODS: This study investigated the role of FENDRR, a lncRNA previously found to be downregulated in NSCL/P, in NSCPO pathogenesis. FENDRR expression in NSCPO tissues was analyzed via RT-qPCR and fluorescence in situ hybridization. Apoptosis in human embryonic palatal mesenchymal (HEPM) cells was assessed using Western blotting, flow cytometry, and TUNEL assays. Bioinformatics, methylation-specific PCR, dual-luciferase reporter assays, and RNA immunoprecipitation were employed to examine FENDRR's interaction with MFN1.
RESULTS: FENDRR was significantly reduced in NSCPO tissues. FENDRR knockdown disrupted mitochondrial dynamics and activated mitochondrial apoptosis in HEPM cells. Mechanistically, FENDRR formed an RNA-DNA triplex with the MFN1 promoter, recruiting TET2 to promote MFN1 transcription via promoter demethylation.
CONCLUSIONS: FENDRR enhances MFN1 expression, maintains mitochondrial fusion, and suppresses apoptosis in HEPM cells. This study provides novel insights into the regulatory role of lncRNAs in NSCPO pathogenesis and identifies FENDRR as a potential therapeutic target.